Publications by authors named "Brunella Capaldo"

36 Publications

Uncooked cornstarch for the prevention of hypoglycemic events.

Crit Rev Food Sci Nutr 2021 Jan 18:1-14. Epub 2021 Jan 18.

Department of Clinical Medicine and Surgery, University of Naples Federico II School of Medicine and Surgery, Naples, Italy.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases - glycogen storage diseases and other rare disorders - and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10408398.2020.1864617DOI Listing
January 2021

Evaluation of cardiovascular risk in adults with type 1 diabetes: poor concordance between the 2019 ESC risk classification and 10-year cardiovascular risk prediction according to the Steno Type 1 Risk Engine.

Cardiovasc Diabetol 2020 10 3;19(1):166. Epub 2020 Oct 3.

Department of Clinical Medicine and Surgery, Federico II University, Via S. Pansini 5, 80131, Naples, Italy.

Background: Patients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D.

Methods: A cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category.

Results: Men had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged < 35 years and 100% of patients ≥ 35 years were at very high/high risk. Conversely, using ST1RE to predict the 10-year CVD risk within each ESC category, among patients at very high risk according to ESC, almost all (99%) had a moderate CVD risk according to ST1RE if age < 35 years; among patients aged ≥35 years, the majority (59.1%) was at moderate risk and only 12% had a predicted very high risk by ST1RE. The presence of target organ damage or three o more CV risk factors, or early onset T1D of long duration (> 20 years) alone identified few patients (< 30%) among those aged ≥35 years, who were at very high risk according to ESC, in whom this condition was confirmed by ST1RE; conversely, the coexistence of two or more of these criteria identified about half of the patients at high/very high risk also according to this predicting algorithm. When only patients aged ≥ 50 years were considered, there was greater concordance between ESC classification and ST1RE prediction, since as many as 78% of those at high/very high risk according to ESC were confirmed as such also by ST1RE.

Conclusions: Using ESC criteria, a large proportion (45%) of T1D patients without CVD are classified at very high CVD risk; however, among them, none of those < 35 years and only 12% of those ≥ 35 years could be confirmed at very high CVD risk by the ST1RE predicting algorithm. More studies are needed to characterize the clinical and metabolic features of T1D patients that identify those at very high CVD risk, in whom a very aggressive cardioprotective treatment would be justified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-020-01137-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533035PMC
October 2020

Continuous glucose monitoring in subjects undergoing bariatric surgery: Diurnal and nocturnal glycemic patterns.

Nutr Metab Cardiovasc Dis 2020 10 11;30(11):1954-1960. Epub 2020 Jul 11.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Background And Aims: Although the use of Continuous Glucose Monitoring (CGM) is rapidly extending, little evidence is currently available on daily glycemic excursions after different bariatric procedures. We assessed glycemic patterns after sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB) using CGM.

Methods And Results: Cross-sectional study in subjects who had undergone RYGB (n = 22) or SG (n = 29) since at least 1 year, without pre-surgery or in current diabetes (T2DM) remission. All subjects underwent 7 day-CGM (Dexcom G4 PLATINUM), which provides glucose variability (GV), number and time spent in hypoglycemia, hypoglycemia patterns (postprandial, nocturnal or mixed). All indexes of GV were higher after RYGB than after SG (p < 0.001). Twenty-eight (55%) subjects experienced hypoglycemia. The number of events was higher after RYGB than SG (p = 0.017) while it did not differ in subjects with or without pre-surgery T2DM (p = 0.129). Overall, 9 (32%) subjects presented hypoglycemia exclusively during the postprandial period, 8 (29%) an exclusively nocturnal pattern and 11 (39%) a mixed pattern. The nocturnal pattern was more frequent after SG than RYGB (53.8% vs 6.7%, p = 0.036) while no difference was observed in subjects with or without pre-surgery T2DM (p = 0.697). Hypoglycemia symptoms were more frequent in subjects with postprandial than in those with nocturnal pattern (77.8% vs 12.5%, p = 0.015).

Conclusions: RYGB is characterized by a greater GV and a higher number of hypoglycemia events mostly post-prandial and symptomatic, while SG is associated with nocturnal and often asymptomatic hypoglycemia. These findings suggest that post-bariatric hypoglycemia is a more complex, not exclusively, postprandial phenomenon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.06.029DOI Listing
October 2020

Adapted recreational football small-sided games improve cardiac capacity, body composition and muscular fitness in patients with type 2 diabetes.

J Sports Med Phys Fitness 2020 Sep 12;60(9):1261-1268. Epub 2020 Jun 12.

Department of Human Movement Sciences and Wellbeing, Parthenope University, Naples, Italy -

Background: The usefulness of adapted small-sided games (SSGs) in improving cardiac function in subjects with T2DM is still debated. Here we evaluated the effects of 18 weeks indoor muscular activation training (6 weeks; IMA) followed by adapted SSGs football training (12 weeks) on cardiac function, muscular fitness, body composition and adiponectin expression in sedentary T2DM volunteers.

Methods: Six T2DM patients underwent IMA protocol of 6 weeks, twice a week followed by 12 weeks SSGs (5-a-side, once a week) training. Glucose, lipid profile and serum homocysteine concentration, body composition (BC), bone mineral density (DEXA), were determined at baseline and after 18 weeks (IMA+SSGs). VO2max and muscular fitness were recorded at baseline and after IMA (6 weeks) and SSGs (12 weeks), respectively.

Results: No significant differences were found for VO2max and muscular fitness after 6weeks of IMA. After 18 weeks (6 weeks IMA + 12 weeks SSGs) of training, significant improvements were found in the following parameters: work capacity, VO2peak, Ventilation (VEpeak), breathing reserve consumption and oxygen uptake efficiency slope (P<0.05); leg fitness (P<0.05), BC (P<0.05), vertebral column T-score (P<0.01) and adiponectin (total and high-molecular-weight; P<0.05). Compared to baseline, a reduction in serum homocysteine occurred after 18 weeks of training (P<0.05).

Conclusions: We evidenced that weekly adapted SSGs friendly football matches for 12 weeks improve cardiorespiratory capacity and the expression of independent markers associated with cardiovascular risk in T2DM patients, suggesting an overall reduced CVD-risk in these patients. These preliminary data encourage us to test the efficacy of this type of exercise in a larger population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0022-4707.20.10498-5DOI Listing
September 2020

Impact of Grape Products on Lipid Profile: A Meta-Analysis of Randomized Controlled Studies.

J Clin Med 2020 Jan 22;9(2). Epub 2020 Jan 22.

Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.

: Growing evidence shows that grape polyphenols can improve cardiovascular risk factors. Although there are clear data supporting a beneficial effect of grape supplementation on blood pressure and glucose metabolism, the effects of grape polyphenols on lipid metabolism are still controversial. : We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of grape products on lipid profile. : A systematic search was performed in the PubMed, Web of Science, Scopus, and EMBASE databases without any language or publication year restriction. The reference lists of all retrieved articles were manually reviewed. RCTs evaluating the impact of grape products/juice/extracts on lipid profile were included. Difference in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), oxidized low-density lipoprotein cholesterol (oxLDL-C), apolipoprotein (apo) A, apo B before and after administration of grape products or placebo were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CI). The impact of clinical and demographic features on effect size was assessed by meta-regression. : The administration of grape products is associated with a significant improvement of lipid profile, as evidenced by changes in TC (MD: -7.6 mg/dL (-0.2 mmol/L); 95% CI: -10.8, -4.4; < 0.001), HDL-C (MD: 1.4 mg/dL (0.04 mmol/L); 95% CI: 0.8, 1.9; < 0.001, I = 74.7%, < 0.001), LDL-C (-6.3 mg/dL (-0.16 mmol/L); 95% CI: -9.5, -3.0; < 0.001), oxLDL-C (MD: -4.5 U/L; 95% CI: -7.5, -1.5; = 0.003, I = 90.6%, < 0.001), apo B (MD: -2.4 mg/dL (-0.05 µmol/L); 95% CI: -4.5, -0.3; p = 0.026), and TG (MD: -14.5 mg/dL (-0.16 mmol/L); 95% CI: -17.7, -11.2; < 0.001) levels in subjects receiving grape products compared to placebo. With regard to the extent of the lipid-lowering effect, compared to baseline values, the highest reduction was reported for LDL-C (MD: -5.6 mg/dL (-0.14 mmol/L); 95% CI: -9.5, -1.7; = 0.005) and for oxLDL-C (MD: -5.0 U/L; 95% CI: -8.8, -1.2; = 0.010, I = 0%, = 0.470). : Grape polyphenols exert a favorable effect on lipid profile in humans by significantly reducing plasma levels of LDL-C and oxLDL-C.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9020313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073656PMC
January 2020

Postprandial Glucose Control in Type 1 Diabetes: Importance of the Gastric Emptying Rate.

Nutrients 2019 Jul 10;11(7). Epub 2019 Jul 10.

Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.

The achievement of optimal post-prandial (PP) glucose control in patients with type 1 diabetes (T1DM) remains a great challenge. This review summarizes the main factors contributing to PP glucose response and discusses the likely reasons why PP glucose control is rarely achieved in T1DM patients. The macronutrient composition of the meal, the rate of gastric emptying and premeal insulin administration are key factors affecting the PP glucose response in T1DM. Although the use of continuous insulin infusion systems has improved PP glucose control compared to conventional insulin therapy, there is still need for further ameliorations. T1DM patients frequently present a delayed gastric emptying (GE) that produces a lower but more prolonged PP hyperglycemia. In addition, delayed GE is associated with a longer time to reach the glycemic peak, with a consequent mismatch between PP glucose elevation and the timing of premeal insulin action. On this basis, including GE time and meal composition in the algorithms for insulin bolus calculation of the insulin delivery systems could be an important step forward for optimization of PP glucose control in T1DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11071559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683017PMC
July 2019

Glycemic control and microvascular complications in adults with type 1 diabetes and long-lasting treated celiac disease: A case-control study.

Diabetes Res Clin Pract 2018 Sep 1;143:282-287. Epub 2018 Aug 1.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. Electronic address:

Aims: To investigate whether in type 1 diabetes (T1DM) patients the concomitance of long-lasting celiac disease (CD) treated with a gluten free diet (GFD) impacts glycaemic control and the prevalence/severity of microvascular complications.

Methods: A case-control, observational study was performed in 34 patients with T1DM and GFD-treated CD and 66 patients with T1DM alone matched for age, gender, and T1DM duration. Anthropometric parameters, glucose control (HbA1), status of chronic complications and concomitant autoimmune diseases were evaluated.

Results: HbA1 level was similar in T1DM + CD and T1DM alone (7.8 ± 1.0 vs 7.7 ± 1.1%, P = 0.57); insulin requirement was significantly higher in T1DM + CD compared with T1DM (P = 0.04). There were no differences in systolic blood pressure while diastolic blood pressure was significantly lower in T1DM + CD (P = 0.003). The prevalence/severity of microvascular complications was similar between the two groups. Glomerular filtration rate (eGFR) was significantly lower in T1DM + CD (100 ± 20 vs 110 ± 16 ml/min/1.73 m, P = 0.007).

Conclusions: In patients with T1DM, the co-occurrence of long-term GFD-treated CD neither worsens glycemic control nor negatively impacts chronic microvascular complications. However, patients with T1DM + CD have lower eGFR values than those with T1DM alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2018.07.031DOI Listing
September 2018

Implementation of Low Glycemic Index Diet Together with Cornstarch in Post-Gastric Bypass Hypoglycemia: Two Case Reports.

Nutrients 2018 May 25;10(6). Epub 2018 May 25.

Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.

Post-bariatric hypoglycemia (PBH) is an increasingly recognized long-term complication of bariatric surgery. The nutritional treatment of PBH includes a high-fiber diet and the restriction of soluble and high-glycemic index carbohydrates; however, these measures are not always enough to prevent hypoglycemia. We evaluated the efficacy of uncooked cornstarch, a low-glycemic index carbohydrate characterized by slow intestinal degradation and absorption, in addition to a high-fiber diet, for the treatment of PBH. We report the cases of two young women suffering from severe postprandial and fasting hypoglycemia following Roux-en-Y gastric bypass (RYGB). The patients underwent Continuous Glucose Monitoring (CGM) before and 12⁻16 weeks after the administration of uncooked cornstarch (respectively 1.25 g/kg b.w. and 1.8 g/kg b.w.) in addition to a high-fiber diet. In both patients, CGM showed more stable glucose levels throughout monitoring, a remarkable reduction of the time spent in hypoglycemia (.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu10060670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024813PMC
May 2018

Gastric Emptying Impacts the Timing of Meal Glucose Peak in Subjects With Uncomplicated Type 1 Diabetes.

J Clin Endocrinol Metab 2018 06;103(6):2269-2276

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Context: Diabetes mellitus is associated with gastrointestinal (GI) motility dysfunction, ranging from delayed to accelerated gastric emptying (GE).

Objective: To evaluate GE in patients with type 1 diabetes mellitus (T1DM) without chronic complications and to investigate its relation with postprandial glucose and GI hormone responses.

Design: Cross-sectional study.

Setting/participants: Forty-two patients with T1DM free of chronic complications referred to Federico II University and 31 healthy controls similar for age, sex, and body mass index.

Interventions/main Outcome Measures: GE was assessed by using the 13C-octanoate breath test with a standardized solid meal. During the meal, plasma glucose, ghrelin, and glucagon-like peptide 1 (GLP-1) responses were assessed, and GI symptoms were evaluated by a specific questionnaire.

Results: Patients with T1DM showed a significantly slower GE half-emptying time (GE t1/2) (113 ± 34 minutes) than did controls (89 ± 17 minutes; P < 0.001). Thirty-six percent of T1DM showed a delayed GE (t1/2 > 120 minutes), whereas all controls showed a normal GE. When patients with T1DM were stratified according to GE t1/2, postmeal glucose response was significantly different between those with delayed and those with normal GE (P = 0.013). In particular, patients with T1DM and delayed GE showed a significantly longer mean time to peak glucose than did patients with normal GE (P = 0.004). In addition, GE t1/2 was an independent predictor of the time to peak glucose (β = 0.329; P = 0.025). GLP-1 and ghrelin responses to the test meal, as well as the prevalence of GI symptoms, were similar between patients with T1DM and controls and between patients with T1DM with normal GE and those with delayed GE.

Conclusions: Delayed GE time is associated with a longer time to peak glucose. GE evaluation could be useful for individualizing the timing of preprandial insulin bolus in patients with T1DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2017-02811DOI Listing
June 2018

Bariatric surgery and long-term nutritional issues.

World J Diabetes 2017 Nov;8(11):464-474

Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.

Bariatric surgery is recognized as a highly effective therapy for obesity since it accomplishes sustained weight loss, reduction of obesity-related comorbidities and mortality, and improvement of quality of life. Overall, bariatric surgery is associated with a 42% reduction of the cardiovascular risk and 30% reduction of all-cause mortality. This review focuses on some nutritional consequences that can occur in bariatric patients that could potentially hinder the clinical benefits of this therapeutic option. All bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal tract; this alteration makes these patients more susceptible to developing nutritional complications, namely, deficiencies of macro- and micro-nutrients, which could lead to disabling diseases such as anemia, osteoporosis, protein malnutrition. Of note is the evidence that most obese patients present a number of nutritional deficits already prior to surgery, the most important being vitamin D and iron deficiencies. This finding prompts the need for a complete nutritional assessment and, eventually, an adequate correction of pre-existing deficits before surgery. Another critical issue that follows bariatric surgery is post-operative weight regain, which is commonly associated with the relapse of obesity-related co-morbidities. Nu-tritional complications associated with bariatric surgery can be prevented by life-long nutritional monitoring with the administration of multi-vitamins and mineral supplements according to the patient's needs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4239/wjd.v8.i11.464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700383PMC
November 2017

Successful Pregnancy in a Young Woman with Multiple Acyl-CoA Dehydrogenase Deficiency.

JIMD Rep 2018 7;39:1-6. Epub 2017 Jul 7.

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Multiple acyl-CoA dehydrogenation deficiency (MADD) is an inborn disorder of fatty acid oxidation due to a defect in electron transfer to the respiratory chain. We describe the medical/nutritional management of a successful pregnancy in a 19-year-old woman with a known diagnosis of MADD. A high-carbohydrate, low-fat, six-meal diet supplemented with protein was prescribed to meet the nutritional needs during pregnancy. L-Carnitine supplementation was also progressively increased over the weeks. Serum acyl-carnitine profile revealed raised levels of chain-length C6-C14, which remained substantially unchanged during pregnancy. Serum amino acid profile was in the normal range indicating an adequate nutritional support. Pregnancy progressed uneventful and the patient gave birth to a healthy boy without any complication.A careful clinical monitoring associated with an adequate medical/nutritional management may improve pregnancy outcome in women with MADD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/8904_2017_38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953900PMC
July 2017

Five-year results of laparoscopic sleeve gastrectomy: effects on gastroesophageal reflux disease symptoms and co-morbidities.

Surg Obes Relat Dis 2016 Jun 26;12(5):960-968. Epub 2015 Sep 26.

Gastrointestinal Unit, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.

Background: Laparoscopic sleeve gastrectomy (LSG) is becoming the most performed bariatric procedure; however, data available on long-term follow-up are scanty.

Objectives: The aim of the present study was to evaluate the 5-year efficacy of LSG on weight loss, gastroesophageal reflux disease (GERD) symptoms, and obesity-associated co-morbidities.

Setting: Tertiary-care referral hospital.

Methods: This study retrospectively analyzed 105 obese patients undergoing LSG from January 2006 to December 2009. The preoperative evaluation included demographic characteristics, evaluation of co-morbidities, a double-contrast barium swallow, and an upper-gastrointestinal endoscopy. The following data were collected at 1, 3, and 5 years after surgery: weight, improvement/remission of co-morbidities, complications, and revisional surgery.

Results: According to preoperative body mass index (BMI), patients were divided into Group 1 (n = 61) with BMI≤50 kg/m(2) and Group 2 (n = 44) with BMI>50 kg/m(2). The follow-up rate was 94% after 5 years (n = 99). Delta BMI (BMI at follow-up-preoperative BMI) was significantly higher in Group 2 than in Group 1 at 1-3 years and 5 years (P<.001). Furthermore, at 5 years, Group 2 showed a significantly higher percentage total weight loss (%TWL) (26.6%±18.3% versus 33.5%±12.9%, P = .006) than Group 1, whereas percentage excess weight loss was similar (58.4%±21.8% versus 55.3%±19.5%, P = .5).Younger age at surgery and absence of postoperative GERD were associated with a better %TWL at 5 years (P<.001 and P = .03).

Conclusion: LSG is an effective procedure at long-term, with good weight loss outcomes and with a considerable improvement of obesity-associated co-morbidities. Younger age at surgery and absence of postoperative GERD were associated with a better %TWL at 5 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2015.09.014DOI Listing
June 2016

A 19 year follow-up of a woman with lipoprotein lipase deficiency treated with biliopancreatic diversion.

Clin Case Rep 2015 Dec 5;3(12):1030-3. Epub 2015 Nov 5.

Department of Clinical Medicine and Surgery Federico II University of Naples Via S. Pansini 5 Naples 80131 Italy.

We show the long-term efficacy and safety of modified biliopancreatic diversion for the treatment of LPL-deficiency. How this option compares with gene therapy is difficult to evaluate due to limited experience. Surgery may be the first option in patients in whom medical therapy is ineffective and gene therapy not applicable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693709PMC
December 2015

Role of the Entero-Insular Axis in the Pathogenesis of Idiopathic Reactive Hypoglycemia: A Pilot Study.

J Clin Endocrinol Metab 2015 Dec 26;100(12):4441-6. Epub 2015 Oct 26.

Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.

Context: Idiopathic reactive hypoglycemia (IRH) is characterized by recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after meals. The underlying mechanisms remain obscure.

Objective: This study aimed to investigate the response of the glucoregulatory and gastrointestinal hormones to an oral glucose load (OGTT) in individuals with documented IRH.

Design And Setting: This was a cross-sectional study composed of outpatients referred to "Federico II" University of Naples.

Patients: We enrolled subjects with IRH documented by a mixed meal under ordinary life conditions and healthy subjects as controls.

Main Outcome Measure: We measured plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), GIP, and glucagon response to a 75-g OGTT in cases and controls.

Results: Ten IRH and eight control subjects were enrolled. During the OGTT, mean plasma glucose tended to be lower in IRH than in control subjects, reaching a statistically significant difference at 240 minutes (T240) (43 ± 1.6 vs 72 ± 0.3 mg/dL; P = .001). Accordingly, the insulin response was higher in IRH than in control subjects (P < .019) with a statistically significant difference (46%) at T90 (P = .045) and was associated with significantly lower glucagon levels in the late phase of the OGTT: at T120 (P = .031) and T180 (P = .048) in IRH than in control subjects. A greater GLP-1 response was found among IRH compared with control subjects (P = .005); GLP-1 peak was 2-fold higher in IRH individuals (9.77 ± 2.52 pmol/L) than in the control group (4.19 ± 0.53 pmol/L; P = .041). In the IRH group, GLP-1 peak inversely correlated with the nadir of plasma glucose (r = -0.66; P = .039). A multivariate analysis confirmed that GLP-1 peak independently predicted the plasma glucose nadir (β = -0.593; P = .026).

Conclusions: GLP-1 may play a significant role in the pathogenesis of idiopathic IRH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2015-3309DOI Listing
December 2015

Long-term follow-up of patients with phenylketonuria treated with tetrahydrobiopterin: a seven years experience.

Orphanet J Rare Dis 2015 Feb 8;10:14. Epub 2015 Feb 8.

Department of Translational Medicine-Section of Pediatrics, Federico II University, Via S. Pansini 5, 80131, Naples, Italy.

Background: Phenylketonuria (PKU) is an autosomal recessive disorder caused by the deficiency of phenylalanine hydroxylase that catalyzes the conversion of phenylalanine to tyrosine, using tetrahydrobiopterin (BH4) as coenzyme. Besides dietary phenylalanine restriction, new therapeutic options are emerging, such as the treatment with BH4 in subgroups of PKU patients responding to a loading test with BH4.

Methods: A no-profit open-label interventional trial with long-term oral BH4 therapy, sponsored by the Italian Medicines Agency (AIFA), was performed in a group of 17 PKU patients resulted as BH4 responders among 46 subjects analyzed for BH4-responsiveness (prot. FARM5MATC7). We report on efficacy and safety data of BH4 therapy and analyze factors predicting BH4-responsiveness and long-term response to BH4. A BH4-withdrawal test was used as a proof of the efficacy of long-term therapy with BH4.

Results: Forty-four percent of the patients responded to the 48 h-long loading test with BH4. All the phenotypic classes were represented. Genotype was the best predictor of responsiveness, along with lower phenylalanine levels at diagnosis, higher tolerance and lower phenylalanine/tyrosine ratio before the test. In BH4 responder patients, long-term BH4 therapy resulted safe and effective in increasing tolerance while maintaining a good metabolic control. The BH4 withdrawal test, performed in a subset of patients, showed that improved tolerance was directly dependent on BH4 assumption. Tolerance to phenylalanine was re-evaluated in 43.5% of patients and was longitudinally analyzed in 5 patients.

Conclusions: Long-term treatment with BH4 is safe and effective in increasing tolerance to phenylalanine. There is real need to assess the actual tolerance to phenylalanine in PKU patients to ameliorate quality of life, improve nutritional status, avoiding unnecessarily restricted diets, and interpret the effects of new therapies for PKU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-015-0227-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351928PMC
February 2015

Cardiometabolic phenotype in children with obesity.

J Pediatr 2014 Dec 17;165(6):1184-9. Epub 2014 Sep 17.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Objectives: To investigate the anthropometric and metabolic correlates of different patterns of left ventricular (LV) geometry in a cohort of outpatient children with high prevalence of obesity.

Study Design: Anthropometric measures, lipid profile, blood pressure (BP), fasting plasma glucose (FPG), and echocardiographic variables were evaluated in 281 white children (6-16 years), of whom 105 were obese and 105 were morbidly obese. Patterns of LV geometry were defined as follows: normal geometry, eccentric LV hypertrophy (LVH), concentric LV remodeling, and concentric LVH.

Results: One hundred forty-eight children exhibited normal LV geometry, 53 eccentric LVH, 36 concentric LV remodeling, and 44 concentric LVH. The 4 groups differed in body mass index, waist circumference, waist-to-height ratio, triglycerides/high-density lipoprotein cholesterol ratio (Tg/HDL-C), and BP (P < .05-.0001). A statistically significant impairment of diastolic function (expressed as greater E/E', P < .002) was observed across patterns of LV geometry. Among anthropometric measures, waist-to-height ratio showed better performance in relation to LVH, with an optimal cut-point of 0.58, compared with body mass index and waist circumference. Children with concentric LVH exhibited the worst metabolic risk profile, with greater prevalence of visceral obesity, high Tg/HDL-C, high BP, and high-normal FPG, than children with normal LV geometry.

Conclusions: In children with high levels of obesity, an unfavorable "cardiometabolic phenotype" can be identified, which includes concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2014.08.007DOI Listing
December 2014

Glomerular filtration rate and cardiometabolic risk in an outpatient pediatric population with high prevalence of obesity.

Obesity (Silver Spring) 2014 Feb;22(2):585-9

Objective: To evaluate the relationship between estimated glomerular filtration rate (eGFR) and cardiometabolic risk factors (CMRF) in an outpatient pediatric population with high prevalence of obesity.

Design And Methods: eGFR was evaluated in 901 children unselected for chronic kidney disease of whom 694 were overweight/obese (6-16 years) and 207 were age- and sex-matched normal weight (NW). We generated three categories of eGFR: mild-low eGFR (< 20th percentile), high eGFR (>80th percentile) and intermediate eGFR (20-80th percentile), considered as the reference category

Results: Children with either mild-low or high eGFR category showed a 2-4 fold higher Odds ratio of high blood pressure, left ventricular hypertrophy, and microalbuminuria compared with children of the intermediate eGFR category. In addition, children with mild-low eGFR levels showed a 1.5-2 fold higher Odds ratio of impaired fasting glucose and high white blood cell count compared with children with intermediate eGFR levels.

Conclusions: In outpatient children with high prevalence of obesity, children with either mildly reduced or high eGFR have an increased burden of CMRF. Children with eGFR < 97 mL/min/1.73 m² show a worse CMR profile. This finding supports the usefulness to assess eGFR to identify children with unfavorable CMR profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.20497DOI Listing
February 2014

Cardiovascular characteristics in subjects with increasing levels of abnormal glucose regulation: the Strong Heart Study.

Diabetes Care 2013 Apr 5;36(4):992-7. Epub 2012 Dec 5.

Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.

Objective: To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.

Research Design And Methods: We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) (age 46-65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).

Results: BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m(2.7) in men) was 3.5 in IFG participants (95% CI 0.68-17.76; P = NS) and 9.76 (2.03-46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.

Conclusions: Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc12-1501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609517PMC
April 2013

Usefulness of the high triglyceride-to-HDL cholesterol ratio to identify cardiometabolic risk factors and preclinical signs of organ damage in outpatient children.

Diabetes Care 2012 Jan 31;35(1):158-62. Epub 2011 Oct 31.

Department of Internal Medicine, S. Maria delle Grazie, Pozzuoli Hospital, Naples, Italy.

Objective: To evaluate whether the high triglyceride-to-HDL cholesterol (TG-to-HDL-C) ratio is associated with cardiometabolic risk (CMR) factors and preclinical signs of organ damage in an outpatient population of white children and adolescents.

Research Design And Methods: The study population included 884 subjects (aged 6-16 years), of whom 206 (23%) were normal weight, 135 (15%) were overweight, and 543 (61%) were obese. Biochemical variables were analyzed in the whole sample, whereas homocysteine and left ventricular (LV) geometry and function were evaluated in 536 and 258 children, respectively.

Results: The percentage of pubertal children (P < 0.001), as well as measurements of BMI, waist circumference, homeostasis model assessment of insulin resistance, white blood cell count, alanine aminotransferase (ALT), systolic blood pressure (P < 0.0001, for all), creatinine (P < 0.001), and diastolic blood pressure (P < 0.02), increased from the lowest to the highest tertile of the TG-to-HDL-C ratio. Age, sex, homocysteine, and glomerular filtration rate did not change. Moreover, interventricular septum thickness, relative wall thickness, and LV mass index (P = 0.01 to P < 0.0001) increased across tertiles of the TG-to-HDL-C ratio. Children with a TG-to-HDL-C ratio ≥2.0 showed a two- to threefold higher risk of elevated ALT levels and concentric LV hypertrophy than those with a TG-to-HDL-C ratio <2.0, independent of confounding factors.

Conclusions: The high TG-to-HDL-C ratio is associated with several CMR factors and preclinical signs of liver and cardiac abnormalities in the outpatient, white pediatric population. Thus, a TG-to-HDL-C ratio ≥2.0 may be useful in clinical practice to detect children with a worsened CMR profile who need monitoring to prevent cardiovascular disease in adulthood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc11-1456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241301PMC
January 2012

Fasting plasma glucose and clustering of cardiometabolic risk factors in normoglycemic outpatient children and adolescents.

Diabetes Care 2011 Jun 15;34(6):1412-4. Epub 2011 Apr 15.

Department of Internal Medicine, Pozzuoli Hospital, Pozzuoli, Naples, Italy.

Objective: To evaluate whether fasting plasma glucose (FPG) within a normoglycemic range is associated with cardiometabolic risk factors (CMRF) among children and adolescents in an outpatient setting.

Research Design And Methods: Subjects (780; age 6-16 years) with FPG <100 mg/dL were divided into tertiles of FPG.

Results: BMI, waist circumference, homeostasis model assessment-insulin resistance, systolic blood pressure, and white blood cell (WBC) count (P < 0.0001) increased across tertiles of FPG. Subjects with high-normal FPG (89-99 mg/dL) showed a higher risk of insulin resistance, hypertension, and high WBC count compared with subjects with low-normal FPG, independent of BMI z score.

Conclusions: In outpatient children and adolescents, higher FPG within the normal range is associated with several CMRF, independent of obesity. Thus the simple measurement of FPG may help identify subjects who warrant some monitoring in relation to cardiovascular risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc10-1783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114352PMC
June 2011

Laparoscopic reinforced sleeve gastrectomy: early results and complications.

Obes Surg 2011 Jun;21(6):783-93

General and Laparoscopic Surgery Unit, San Giovanni Bosco Hospital, Naples, Italy.

Background: Sleeve gastrectomy (SG) was pioneered as a two-stage intervention for super and super-super obesity to minimize morbidity and mortality; it is employed increasingly as a primary procedure. Early outcomes and integrity of laparoscopic SG (LSG) against leak using a technique incorporating gastric transection-line reinforcement were studied.

Methods: Between 2003 and 2009, 121 patients underwent LSG (16, two-stage; 105, primary). Of the patients, 66% were women, mean age 38.8 ± 10.9 (15.0-64.0), and body mass index (BMI, kg/m(2)) 48.7 ± 9.3 (33.7-74.8). Bovine pericardium (Peri-Strips Dry [PSD]) was used to reinforce the staple line. Parametric and nonparametric tests were used, as appropriate. The paired t test was used to assess change from baseline; bivariate analyses and logistic regression were used to identify preoperative patient characteristics predictive of suboptimal weight loss.

Results: Mean operative time was 105 min (95-180), and mean hospitalization was 5.6 days (1-14). There was no mortality. There were 6 (5.0%) complications: 1 intraoperative leak, 1 stricture, 1 trocar-site bleed, 1 renal failure, and 2 wound infections. There were no postoperative staple-line leaks. Following 15 concomitant hiatal hernia operations, 3 (20%) recurred: 1 revised to RYGB and 2 in standby. Two post-LSG hiatal hernias of the two-stage series required revisions because of symptoms. BMI decreased 24.7% at 6 months (n = 55) to 37.5 ± 9.3 (22.2-58.1); %EWL was 48.1 ± 19.3 (15.5-98.9). Twelve-month BMI (n = 41) was 38.4 ± 10.5 (19.3-62.3); %EWL was 51.7 ± 25.0 (8.9-123.3). Forty-eight-month BMI (n = 13) was 35.6 ± 6.8 (24.9-47.5); %EWL was 61.1 ± 12.2 (43.9-82.1) (p < 0.001). Preoperative BMI was predictive of >70% of patients who experienced <50% EWL at 6 months. At 2 weeks, 100% of type 2 diabetes patients (n = 23) were off medication (mean HbA(1C), 5.9 ± 0.5%; glycemia, 90.0 ± 19.9 mg/dL (p < 0.01) at 3 months).

Conclusions: Laparoscopic PSD-reinforced LSG as a staged or definitive procedure is safe and effective in the short term and provides rapid type 2 diabetes mellitus reduction with a very low rate of complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11695-011-0400-7DOI Listing
June 2011

Preclinical manifestations of organ damage associated with the metabolic syndrome and its factors in outpatient children.

Atherosclerosis 2010 Dec 23;213(2):611-5. Epub 2010 Oct 23.

Department of Internal Medicine, Pozzuoli Hospital, via Domitiana Loc. La Schiana, 80078 Pozzuoli, Napoli, Italy.

Background: To evaluate whether the pediatric metabolic syndrome (MetS) or its factors are useful to detect subclinical abnormalities of cardiac, liver, and glomerular damage in an outpatient population.

Methods: The population study included 799 children (age 10 ± 3 years, mean ± SD), 24% of whom were normalweight, 25% overweight, and 51% obese. Alanine-aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR) and HOMA-IR were analyzed in all children. Microalbuminuria (MA) and left ventricular (LV) geometry and function were evaluated in 501 and 247 children, respectively. MetS was defined using Cook's criteria.

Results: MetS was diagnosed in 131 children (16%). Children with MetS+ and MetS- were similar for age, gender and Tanner stage distribution. Children with MetS+ showed higher ALT levels (31 ± 19 vs 21 ± 11 IU/L, p<0.0001), LV mass (39 ± 10 vs 34 ± 10 g/h(2.7), p<0.001) and relative wall thickness (0.37 ± 0.06 vs 0.35 ± 0.05, p<0.01) than MetS-. The two groups were similar for MA and eGFR. At multiple logistic regression analysis, children MetS+ showed a higher risk (OR, 95% Cl) adjusted for confounding factors, of high ALT levels (1.71, 1.12-2.59, p=0.012) and concentric LV hypertrophy (2.17, 1.01-4.66, p=0.047) than children MetS-. The risk of preclinical liver and cardiac damage associated with the MetS phenotype was not higher than predicted by its single components.

Conclusions: Children with MetS show a 2-fold greater risk of having high ALT levels and concentric LV hypertrophy. However, the risk of subclinical manifestations of liver and cardiac damage can be predicted equally well by the single components of the syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2010.09.017DOI Listing
December 2010

Prehypertension in outpatient obese children.

Am J Hypertens 2009 Dec 10;22(12):1309-13. Epub 2009 Sep 10.

Department of Internal Medicine, S. Maria delle Grazie, Pozzuoli Hospital, Naples, Italy.

Background: The aim of the study was to analyze the prevalence of prehypertension (PH) in obese (OB) children and its relation with estimated glomerular filtration rate (eGFR) and left ventricular (LV) function.

Methods: The study included 447 OB and 131 normal-weight children. PH was defined according to the criteria proposed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Insulin sensitivity was evaluated by HOMA(IR), and eGFR was calculated by Schwartz's formula. LV function was analyzed by echocardiography in 165 OB children.

Results: PH was observed in 79 OB children (17.7%) and in 2 (1.5%) controls. Among OB children, those with PH had greater percentage of males (P < 0.05), higher level of body mass index (BMI) (P < 0.001), waist circumference (WC) (P < 0.005), and HOMA(IR) (P < 0.001), compared to PH- children. The two groups did not differ for eGFR and LV function. At logistic regression analysis, PH was independently associated with male gender (P < 0.025) and HOMA(IR) (P < 0.002). Gender analysis showed that boys with PH presented higher levels of BMI (P < 0.005), WC (P < 0.01), HOMA(IR) (P < 0.001), and triglycerides (P < 0.005) compared to PH- boys. Females with PH were older and in more advanced postpubertal stage, had higher BMI, WC (P < 0.05, for all), and HOMA(IR) (P < 0.025), compared to PH- girls.

Conclusions: In a population of outpatient OB children, the prevalence of PH was 17.7% and boys were more likely than girls to have PH. This condition is characterized by insulin resistance in both sexes but no impairment in glomerular and LV function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ajh.2009.175DOI Listing
December 2009

Management of type 2 diabetic patients attending diabetic outpatient clinics compared with those cared for by the general practitioners: an experience of integrated diabetes management.

Ann Ist Super Sanita 2009 ;45(2):162-7

Dipartimento di Medicina Interna, Ospedale S. Maria delle Grazie, Naples, Italy.

To improve the quality of diabetes care, a project of integrated diabetes management (PIDM) involving some general practitioner (GPs) has been recently undertaken. The purpose of this study is to compare features and treatment of patients followed by diabetic outpatient clinics (DOCs) with those cared for by GPs trained to the PIDM. Twenty-one DOCs and eleven GPs participated in the study. Patients followed by DOCs (n. = 1110) showed longer duration of diabetes, higher prevalence of metabolic syndrome than patients followed by GPs (n. = 305). More patients followed in DOCs performed insulin therapy, while a lower number received ACE /angiotensin blockers, antiplatelet, lipid lowering drugs and multifactorial intervention than patients followed by GPs. The proportion of patients in good control for glucose, pressure and lipid levels was similar in the two groups. Conversely, a higher number of patients attending DOCs were in poor glycemic, pressure, and lipid control compared with patients followed by GPs. In conclusions, PIDM provides satisfactory results in terms of overall glucose, pressure and lipid control, thus encouraging implementation of PIDM to meet the increasing demand for diabetes care.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2009

Association of elevated serum alanine aminotransferase with metabolic factors in obese children: sex-related analysis.

Metabolism 2009 Mar;58(3):368-72

Department of Internal Medicine, S. Maria delle Grazie, Pozzuoli Hospital, 80078 Naples, Italy.

Alanine aminotransferase (ALT) elevations are considered a surrogate marker of nonalcoholic liver disease and predict later development of diabetes and metabolic syndrome in adults. The aim of the present study is to evaluate the prevalence of high ALT levels in obese children using updated and sex-related cutoff ALT value (ALT >30 IU/L for boys and >19 IU/L for girls). We also analyzed the association between ALT levels and metabolic factors in the 2 sexes. Three-hundred fifty-eight obese children (168 boys and 190 girls; age range, 6-16 years) were studied. Inclusion criteria were as follows: obesity, defined by an individual body mass index (BMI) greater than or equal to the 95th percentile for age and sex; negativity of markers for viral hepatitis; and no alcohol consumption. Two hundred six nonobese children (92 boys and 114 girls; age range, 6-16 years) served as a control group for ALT levels. The percentage of obese children with elevated ALT was 36% in boys and 55% in girls. Obese boys with ALT greater than 30 IU/L showed higher mother's BMI (P < .025), BMI, waist circumference, insulin resistance evaluated with homeostasis model assessment (HOMA-IR) index (P < .0001, for all), and systolic and diastolic blood pressure (P < .025, for both) compared with those with ALT not exceeding 30 IU/L. The ALT levels correlated positively with mother's BMI, BMI, waist circumference, HOMA-IR, triglycerides, and blood pressure. In linear regression analysis, waist circumference was the only independent factor associated with ALT level (beta = 0.370, t = 3,905, P < .0001). Obese girls with ALT greater than 19 IU/L exhibited lower age (P < .025) and higher triglycerides (P < .0001) than girls with ALT not exceeding 19 IU/L. The ALT levels correlated positively with triglycerides and HOMA-IR and negatively with age and Tanner stage. In linear regression analysis, ALT levels were independently associated only with triglycerides (beta = 0.330, t = 4.588, P < .0001). Our study shows that a high proportion of obese children present elevated ALT levels. This abnormality is associated in boys, more than in girls, with preclinical traits of the metabolic syndrome. The adoption of sex-related cutoff of ALT levels is desirable also for the pediatric population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2008.10.010DOI Listing
March 2009

Hyperinsulinemia and insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects. The GISIR database.

Nutr Metab Cardiovasc Dis 2008 Nov 3;18(9):624-31. Epub 2007 Dec 3.

University of Verona, Verona, Italy.

Background And Aims: We evaluated whether hyperinsulinemia and/or insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects.

Methods And Results: A database of non-diabetic Italian subjects has recently been set up using data from hyperinsulinemic euglycemic clamp studies carried out using the standard technique (40 mU per min per square meter of body surface area). In this database we evaluated the relationships between fasting plasma insulin (FPI), glucose metabolized during clamp (M) and plasma levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), uric acid (UA) as well as blood pressure (BP) in non-diabetic subjects with fasting plasma glucose <6.1 mmol/l. Parallel analyses were conducted in all subjects in the database (n=1093) and in those with all variables available (n=309). In the univariate analysis both FPI and M were significantly correlated with TG, HDL-C, UA and BP (systolic, diastolic and mean). Multivariate regression analyses including center, sex, age, body mass index (BMI), FPI and M as independent variables showed that: (1) TG and UA were positively correlated with FPI and negatively correlated with M; (2) HDL-C was negatively correlated with FPI and positively correlated with M; and (3) BP was negatively correlated with both FPI and M. Analyses of covariance showed that, after adjusting for center, sex, age and BMI, subjects with isolated hyperinsulinemia or isolated insulin resistance had higher TG and UA and lower HDL-C. Subjects with isolated insulin resistance had also higher BP whereas subjects with isolated hyperinsulinemia had lower BP. Subjects with both defects had a worse profile.

Conclusions: Hyperinsulinemia and insulin resistance might contribute with distinct and independent mechanisms to the development of several metabolic and hemodynamic disorders often clustering in the same individual. In particular, hypertriglyceridemia, low HDL-cholesterol and hyperuricemia seem to be related to both hyperinsulinemia and insulin resistance, whereas hypertension seems to be related only to insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2007.05.002DOI Listing
November 2008

Determinants of reduction of coronary flow reserve in patients with type 2 diabetes mellitus or arterial hypertension without angiographically determined epicardial coronary stenosis.

Am J Hypertens 2007 Dec;20(12):1283-90

Department of Clinical and Experimental Medicine, Federico II University Hospital of Naples, Naples, Italy.

Background: Coronary flow reserve (CFR) may be reduced even in the absence of coronary artery disease. We investigated the determinants of CFR impairment in Type 2 diabetes mellitus (DM2) and in arterial hypertension (HTN) without epicardial coronary artery stenosis.

Methods: Twenty-eight patients with DM2 and 27 with HTN, both with normal coronary angiography, and 18 healthy controls underwent transthoracic echocardiography, including Doppler recording of the distal left anterior descending artery, at rest as well as after high-dose dipyridamole. Coronary flow reserve was calculated as the hyperemic to resting coronary diastolic peak velocities ratio.

Results: The three groups were comparable for sex, age, and heart rate. Systolic and mean blood pressures were higher in DM2 and HTN patients than in control subjects. Diabetic and hypertensive patients had a higher left-ventricular mass index (LVMi) and relative wall thickness, impaired diastolic indexes, and lower CFR compared with control subjects (P = .02 and P = .03, respectively) because of lower hyperemic coronary velocity (P = .005 and P = .004, respectively). After a multilinear regression analysis (using age, sex, HTN status, DM2 status, smoking, total cholesterol/HDL-cholesterol ratio, and LVMi as potential determinants), the LVMi increase was the main predictor of the reduction of CFR, adjusted for mean BP (P < .0001), in the pooled population, with a minor contribution of age (P = .03), HTN status (P = .02), and DM2 status (P = .03).

Conclusions: In Type 2 DM and HTN without epicardial coronary stenosis, an impairment of CFR is demonstrable. This is partly explained by an increased left-ventricular mass, able to condition the hyperemic stimulation of myocardial blood flow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjhyper.2007.08.005DOI Listing
December 2007

Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation.

Diabetes Res Clin Pract 2008 Feb 8;79(2):262-8. Epub 2007 Nov 8.

Division of Cardiology, Ospedale dei Pellegrini, ASL-Napoli 1, Naples, Italy.

Objectives: Left ventricular (LV) diastolic dysfunction is considered the earliest manifestation of diabetic cardiomyopathy. Whether LV abnormalities identified at rest by echocardiography predict peak exercise LV performance in uncomplicated type 1 diabetes mellitus (DM1) is largely unknown.

Research Design And Methods: We evaluated LV size, mass, and functions and peak exercise LV performance in 25 subjects with uncomplicated DM1 (median disease duration 13.5 years, 1-30 years) and in 56 non-DM subjects (24 hypertensive (HT) and 32 normotensive (NT)). Overt coronary heart disease, significant microangiopathy and central autonomic neuropathy were minimized by exclusion criteria. Peak exercise LV stroke index (SVi), cardiac index (COi), LV ejection fraction (EF), LV end-diastolic and end-systolic volumes were assessed noninvasively. No subject was on cardiovascular medications at the time of evaluation.

Results: In our study, DM1 did not show LV hypertrophy or impaired LV systolic function at rest. Prevalence of diastolic dysfunction was 8% among DM1, 18% among NT and 50% among HT. Pre-exercise heart rate, SVi, COi, and peak exercise blood pressure (BP) and heart rate were comparable among the three groups, but peak exercise LV EF, SVi and COi were lower in DM1 than in HT and NT independent to covariates (p<0.05). In separate analyses, DM1 predicted lower peak exercise SVi (B=-6.2) and COi (B=-1.6, both p<0.05) independently. Within DM1, glycated haemoglobin (HbA1c) and disease duration did not predict peak exercise LV systolic function.

Conclusions: Our study suggests that uncomplicated DM1 may be associated with subnormal LV contractility reserve, which might not be predicted by LV dysfunction evaluated at rest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2007.09.014DOI Listing
February 2008